Effect of dietary supplementation with Lactobacillus helveticus R0052 on seizure thresholds and antiseizure potency of sodium valproate in mice

Psychopharmacology · 8 authors, 5 centres

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TL;DR

The probiotic significantly increased the threshold for 6 Hz-induced psychomotor seizures and slightly increased thresholds in the ivPTZ test, but did not affect other seizure types or the antiseizure potency of sodium valproate.

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It did not alter the antiseizure potency of valproate in the scPTZ test, though it increased serum valproate concentration. No significant effects were observed on anxiety-related behavior, motor coordination, neuromuscular strength, or locomotor activity. The supplementation increased cecal concentrations of total short-chain fatty acids (SCFAs), acetate, and butyrate.

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other

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preclinical research

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ORIGINAL PAPER

PMC10805985

Effect of dietary supplementation with Lactobacillus helveticus R0052 on seizure thresholds and antiseizure potency of sodium valproate in mice

Psychopharmacology

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ABSTRACT

Abstract Objective Both animal and human studies, though limited, showed that multi-strain probiotic supplementation may reduce the number of seizures and/or seizure severity. Here, we evaluated the effect of a single strain probiotic supplementation on seizure susceptibility, antiseizure efficacy of sodium valproate, and several behavioral parameters in mice. Methods Lactobacillus helveticus R0052 was given orally for 28 days. Its influence on seizure thresholds was evaluated in the iv PTZ- and electrically-induced seizure tests. The effect on the antiseizure potency of valproate was assessed in the sc PTZ test. We also investigated the effects of probiotic supplementation on anxiety-related behavior (in the elevated plus maze and light/dark box tests), motor coordination (in the accelerating rotarod test), neuromuscular strength (in the grip-strength test), and spontaneous locomotor activity. Serum and brain concentrations of valproate as well as cecal contents of SCFAs and lactate were determined using HPLC method. Results L. helveticus R0052 significantly increased the threshold for the 6 Hz-induced psychomotor seizure. There was also a slight increase in the threshold for myoclonic and clonic seizure in the iv PTZ test. L. helveticus R0052 did not affect the threshold for tonic seizures both in the maximal electroshock- and iv PTZ-induced seizure tests. No changes in the antiseizure potency of valproate against the PTZ-induced seizures were reported. Interestingly, L. helveticus R0052 increased valproate concentration in serum, but not in the brain. Moreover, L. helveticus R0052 did not produce any significant effects on anxiety-related behavior, motor coordination, neuromuscular strength, and locomotor activity. L. helveticus R0052 supplementation resulted in increased concentrations of total SCFAs, acetate, and butyrate. Conclusions Altogether, this study shows that a single-strain probiotic – L. helveticus R0052 may decrease seizure susceptibility and this effect can be mediated, at least in part, by increased production of SCFAs. In addition, L. helveticus R0052 may affect bioavailability of valproate, which warrants further investigations. Keywords: Gut-microbiota-brain axis, Psychobiotic, Excitation/inhibition balance, Anticonvulsant, Microbiota-derived metabolites

CITATION EXPORT

Piotr Wlaź, Adrian Wiater, Małgorzata Majewska et al.. Effect of dietary supplementation with Lactobacillus helveticus R0052 on seizure thresholds and antiseizure potency of sodium valproate in mice. Psychopharmacology. (2023). https://doi.org/10.1007/s00213-023-06489-2

AUTHORS

8 · 5 CENTRES

Piotr Wlaź, Adrian Wiater, Małgorzata Majewska, Elżbieta Wyska, Marcin Grąz, Joanna Śliwa-Dominiak, Nikola Gapińska, Katarzyna Socała

1Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL 20–033, Lublin, Poland
2Department of Industrial and Environmental Microbiology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL 20–033, Lublin, Poland
3Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Medyczna 9, PL 30–688, Kraków, Poland
4Department of Biochemistry and Biotechnology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL 20–033, Lublin, Poland
5R&D and Scientific Department, Sanprobi Sp. z o.o Sp.k., Quality Control and Microbiology Laboratory, Kurza Stopka 5/C, PL 70-535 Szczecin, Poland